Banca de DEFESA: ALLANNY ALVES FURTADO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ALLANNY ALVES FURTADO
DATE: 29/01/2021
TIME: 14:00
LOCAL: Videoconferência
TITLE:

STRUCTURAL ANALYSIS AND EVALUATION OF BIOLOGICAL ACTIVITIES OF STIGMURINA ANALOGS PEPTIDES

KEY WORDS:

Tityus stigmurus, Scorpion, Antimicrobial Peptides, Multifunctional Peptides, Cationic Peptides.

PAGES: 116
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Resistance to antimicrobials and antineoplastic agents is considered a worldwide public health problem and the search for new molecules that are more effective or that supplement existing therapies is necessary. In this context, Stigmurin, a peptide native to the venom of scorpion Tityus stigmurus, showed antibacterial activity on gram-positive bacteria, with antiproliferative effect on different cancer cells, low toxicity in human erythrocytes in vitro and trypanocidal activity on Trypanossoma cruzi. In order to expand the potential of the native peptide, analogs to Stigmurin were designed and analyzed for structure and different biological activities. The structural analysis of the analogs peptides, called StigA8 and StigA18, was obtained by structural prediction, molecular modeling and circular dichroism. In vitro biocompatibility was evaluated in human red cells, murine fibroblasts and in vivo in Galleria mellonella moth larvae. The antibacterial activity against gram-positive and gram-negative strains was performed by microdilution in broth and the antibiofilm activity by the microtiter plate and analyzed by scanning electron microscopy, as well as the antibacterial effect in vivo on G. mellonella larvae infected with Staphylococcus aureus. The antiparasitic action of analogs peptides on the epimastigote and trypomastigote forms of T. cruzi was evaluated by counting viable cells and the antiproliferative effect in cancer cell lines was evaluated by the 3-(4,5-dimethylthiazole-2-yl)-2,5- diphenyl-tetrazolium (MTT) salt reduction method. StigA8 and StigA18 showed higher rates of cationicity (+4 and +5, respectively) and hydrophobic moment (0.652 and 0.708, respectively) in relation to the prototype molecule (+2 and 0.571, respectively) and a conformation mostly in α-helix in environments that mimic biological membranes. In addition, peptides showed hemolytic activity of 11.5-22% in a concentration range of 9.37-150 µM, with a cytotoxicity index in murine fibroblasts of 50% at a concentration of 20 µM and 12.3 µM for StigA8 and StigA18, respectively. In addition, no signs of toxicity were observed on G. mellonella larvae at a dose of 120 mg/kg. Both analog peptides showed significant antibacterial activity in strains of gram-positive and negative bacteria in concentrations ranging from 0.93-9.37 µM, with antibiofilm action against S. aureus in concentrations of 7.5-12.5 µM, causing damage such as matrix destruction, cell membrane invaginations, roughness and reduction of the cell diameter by 12.5 µM. StigA8 and StigA18 showed antibacterial effect in vivo, increasing larval survival at 120 mg/kg by 75% and 60%, respectively, at the peak of infection. Trypanocidal activity on the epimastigote and trypomastigote forms of T. cruzi was observed at 6.25 µM for both peptides and antiproliferative potential from the concentration of 2 µM for StigA8 and 4 µM for StigA18. Therefore, StigA8 and StigA18 are molecules with the potential for the development of new antimicrobial and anticancer drugs

BANKING MEMBERS:
Externa à Instituição - FERNANDA CALHETA VIEIRA PORTARO - IB/SP
Presidente - 1544647 - MATHEUS DE FREITAS FERNANDES PEDROSA
Externo à Instituição - RAFAEL MATOS XIMENES - UFPE
Interna - 2085604 - SUSANA MARGARIDA GOMES MOREIRA
Interno - 2213126 - VALTER FERREIRA DE ANDRADE NETO